Cox-2 drugs, like Celebrex, less safe than Cox-1 drugs, like naproxen, study says
MONDAY, Nov. 3 (HealthDay News) -- The increased risk of heart attack that comes with the use of nonsteroidal anti-inflammatory drugs (NSAIDs) to treat arthritis pain is directly related to the specific pain-causing molecule they act against, a new study finds.
"We found a significant correlation between the degree of inhibition in vitro [in the laboratory] of whole blood cox-2, but not whole blood cox-1," said the report by researchers in Spain and Italy.
Cox-1 and cox-2 are different forms of cyclooxygenase, an enzyme whose activity increases inflammation and pain. Older NSAIDs, such as ibuprofen and naproxen, act primarily against cox-1. A newer generation of NSAIDs that act against cox-2 reduce the gastrointestinal bleeding, pain and inflammation that are major side effects of the cox-1 drugs, but they have been found to increase the risk of heart attack and stroke.
Three cox-2 inhibitor NSAIDs have been marketed in the United States. Two of them -- Bextra and Vioxx -- were withdrawn from the market earlier this decade because of their association with an increased risk of heart attack and stroke. A third cox-2, Celebrex, remains available, but with a label warning of cardiovascular risk.
All NSAIDs increase heart risk, according to the new study of 8,852 people who had heart attacks. And the increase was related to both the dosage and the length of time the drugs were taken. But the risk was increased by 18 percent by drugs acting primarily against cox-1, compared to a 60 percent increase for those with the greatest cox-2 activity.
The findings were published in the Nov. 11 issue of the Journal of the American College of Cardiology.
Dr. Michael E. Farkouh, director of clinical trials at the Mount Sinai Cardiovascular Institute in New York City, said the new study "lends support to the theory that each drug must be judged on an individual basis."
The cox-2 impact is an important factor in NSAID cardiovascular risk, but other drug characteristics, some not discussed in the new study, are important as well, Farkouh said.
"What they [the study authors] don't account for is the rise in blood pressure," he said. "Drugs that raise blood pressure are the most toxic. Also important is the half-life of a drug -- how long it stays in the system. They [the authors] don't address that head-on, but they do look at slow release as a variable, which is associated with half-life."
Then there are the possible interactions of a drug with aspirin, which is also widely used for pain relief, Farkouh noted. "The take-home message to patients is that when they are given one of these drugs, they should assess it in terms of all these variables," he said.
Farkouh's view is that "naproxen is the safest drug we have. Its risk profile appears to be consistently low." And while "the jury is still out on Celebrex, it still can have a role in patients at high risk of gastrointestinal bleeding," he said.
Dr. James Brophy, a professor of medicine and epidemiology at McGill University in Montreal who has done NSAID studies, said the new findings "are totally consistent with what has been seen both in clinical trials and observational studies."
The study is yet another signal from a large, real-world database that NSAID use can lead to increased cardiovascular risk, Brophy said.
To learn more about NSAIDs, visit the U.S. Food and Drug Administration.
SOURCES: Michael E. Farkouh, M.D., director, clinical trials, Mount Sinai Cardiovascular Institute, New York City; James Brophy, M.D., professor, medicine and epidemiology, McGill University, Montreal; Nov. 11, 2008, Journal of the American College of Cardiology
All rights reserved